Trulicity ® (dulaglutid) injektion

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Trulicity® (dulaglutid): Statistisk analys av studien för kardiovaskulära utfall

Det primära resultatet av den långsiktiga studien för kardiovaskulära utfall med dulaglutid utvärderades med hjälp av analyser av tid till första förekomst.

Detailed Information

The REWIND study was an event-driven, randomized, double-blind, phase 3 CV outcomes study of dulaglutide.1

The study evaluated the effect on MACE-3 and other serious outcomes with once-weekly dulaglutide 1.5 mg treatment compared with placebo when added to standard of care in participants 50 years of age and older with T2DM and previous CV disease and/or risk CV risk factors.1

The primary outcome was evaluated by time-to-event analyses.2

The Cox proportional hazards regression model was used to estimate HR and calculate 95% CI. The statistical significance of the effect of the intervention was based on the p value from the Cox model. To adjust for alpha spent during a prespecified interim analysis and to maintain overall Type I error of 0.05, the final 2-sided p-value for superiority was 0.0467.2

Key secondary objectives followed a prespecified graphical statistical approach for multiple comparisons to control the overall Type I error rate at a 2-sided α-level of 0.05 (adjusted for interim analysis). With this approach, sharing of alpha according to the prespecified scheme was used to determine statistical significance of the individual components of the primary endpoint and the other key secondary endpoints.2

The median follow-up time in REWIND was 5.4 years.2

Dulaglutide 1.5 mg significantly reduced MACE-3 when compared to placebo (HR=0.88 [95% CI 0.79-0.99]; p=.026), demonstrating a decrease in CV events and showing safety in a population that included a majority of participants without established CV disease.2

Numbers Needed to Treat

The NNT is the estimated number of patients to be treated with a particular therapy for a certain duration to prevent one event. The NNT depends on the characteristics of the study, specifically the study design and outcome variables.3

NNTs must not be compared across different studies, given the differences in populations and follow-up period. They are specific to the population studied. This implies that the same drug may have different NNTs in different study populations.3

Furthermore, when the NNT is calculated, the treatment exposure duration of interest should also be specified since the NNT calculation depends on the exposure duration.3

The REWIND NNTs can be found in Table 1. 2,4

Table 1. Dulaglutide Cardiovascular Outcome Trial Numbers Needed to Treat 2,4

Parameter

Dulaglutide (events/100 pt yrs)

Placebo (events/100 pt yrs)

NNT

Overall REWIND population

2.35

2.66

60

History of CVD a

Yes

3.70

4.20

37

No

1.70

2.00

62

Prior CV Event b

Yes

3.96

4.99

18

No

1.96

2.11

123

Abbreviations: CV = cardiovascular; CVD = cardiovascular disease; ECG = electrocardiogram; MI = myocardial infarction; NNT = number needed to treat; PCI = percutaneous coronary intervention; pt = patient; REWIND = Researching cardiovascular Events with a Weekly Incretin in Diabetes; UA = unstable angina.

a History of CVD is defined as a history of MI, history of myocardial ischemia by a stress test or with cardiac imaging, ischemic stroke, coronary, carotid or peripheral artery revascularization, UA, hospitalization for UA with ECG changes (new or worsening ST or T wave changes), myocardial ischemia on imaging, or need for PCI.

b Post hoc subgroup of prior MI or ischemic stroke

Annual Rate Difference = R placebo- R dulaglutide = 2.66 - 2.35 = 0.31 events/100 patient years = 0.0031 events/patient year

References

1. Gerstein HC, Colhoun HM, Dagenais GR, et al. REWIND Trial Investigators. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20(1):42-49. https://doi.org/10.1111/dom.13028

2. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019;394(10193):121-130. https://doi.org/10.1016/S0140-6736(19)31149-3

3. Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Eng J Med. 1988;318:1728-1733. https://doi.org/10.1056/NEJM198806303182605

4. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

AE = adverse event

CV = cardiovascular

HR = hazard ratio

MACE-3 = major adverse cardiovascular events (death due to cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke)

NNT = number needed to treat

REWIND = Researching cardiovascular Events with a Weekly INcretin in Diabetes

T2DM = type 2 diabetes mellitus

Datum fӧr senaste ӧversyn 2020 M05 05


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